Figure 2.
Models for the trafficking and regulation of prenylated proteins. The farnesyl group is depicted here to represent prenylation. A) The prenylation of a Caax-containing protein is catalyzed by FTase or GGTase-I in the cytsosol. Next it is trafficked to the ER where it is proteoylzed by a CaaX protease such as Rce1 and carboxymethylated by isoprenylcysteine methyltransferase (ICMT). If the protein contains another cysteine near the C-terminus, a protein acyltransferase (PAT) can catalyze the palmitoylation of the protein at the Golgi. Then, the modified protein is trafficked to the plasma membrane. A protein acylthioesterase (APT) can catalyze the removal of the palmitoyl group, allowing for regulation of proteins between different cellular compartments. B) The SmgGDS-607 isoform and possibly a GEF-like protein may interact with an unmodified CaaX protein containing a polybasic region (PBR), promote GDP/GTP exchange, and allow the CaaX protein to enter the prenylation pathway. Once prenylated by GGTase-I or FTase, SmgGDS-558 may facilitate the release of the protein from the prenyltransferase and/or traffic the protein to the ER where it is subsequently proteolyzed and methylated. SmgGDS-558 may also transport the fully processed prenylated protein to and from the plasma membrane.
